Abstract
We have recently found that GPR120, which is abundantly expressed in intestine, functions as a receptor for unsaturated long-chain free fatty acids (FFAs) and that GPR120 stimulation promotes the secretion of glucagons-like peptide-1 (GLP-1) in the mouse (Hirasawa et al., Nat Med 11:90–94, 2005). In this study, we cloned and characterized rat GPR120 (rGPR120), and then we examined the in vivo effects of acute and long-term administration of the natural ligand α-linolenic acid (α-LA). The cloned rat GPR120 complimentary DNA had a seven transmembrane structure, and a homology comparison of human, mouse, and rat GPR120 revealed that the rat GPR120 (rGPR120) shares 85 and 98% sequence identity with the human and mouse GPR120 proteins, respectively. The tissue distribution and ligand properties of rGPR120 were similar to those of mouse GPR120. In addition, α-LA provoked a transient increase in [Ca2+]i levels in HEK293 cells expressing rGPR120. Furthermore, administration of α-LA to the rat increased plasma GLP-1 levels, and long-term administration of α-LA led to proliferation of pancreatic β cells, probably because of the enhanced GLP-1 secretion. These results show that rat GPR120 is a G-protein-coupled receptor whose ligand is a free fatty acid, and it may play an important role in the FFA-associated physiological responses.
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Abbreviations
- FFA:
-
free fatty acid
- FFAR:
-
free fatty acid receptor
- GPCR:
-
G-protein-coupled receptor
- GLP-1:
-
glucagon-like peptide-1
- α-LA:
-
α-linolenic acid
- OA:
-
octanoic acid
- rGPR120:
-
rat GPR120
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Acknowledgments
This work was supported in part by a research grant from the Scientific Fund of the Ministry of Education, Culture, Sports, Science and Technology of Japan (T.A., T.-a.K., A.H., G.T.); the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO; G.T.,A.H.,T.-a.K.); the 21st Century COE Program “Knowledge Information Infrastructure for Genomic Science” (T.T., T.A., G.T.); the Ajinomoto Amino Acid Research Program (G.T.); the grant of Practical Application Research from Science and Technology Incubation Program in Advanced Regions of Japan Science and Technology Agency (G.T.); and the Mitsubishi Foundation (G.T.).
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Toshiki Tanaka, Takeaki Yano, and Tetsuya Adachi equally contributed to this study.
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Tanaka, T., Yano, T., Adachi, T. et al. Cloning and characterization of the rat free fatty acid receptor GPR120: in vivo effect of the natural ligand on GLP-1 secretion and proliferation of pancreatic β cells. Naunyn-Schmied Arch Pharmacol 377, 515–522 (2008). https://doi.org/10.1007/s00210-007-0250-y
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DOI: https://doi.org/10.1007/s00210-007-0250-y